title: Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial.
abstract: OBJECTIVE
  Sentinel lymph node (SLN) surgery provides reliable nodal staging information with less morbidity than axillary lymph node dissection (ALND) for patients with clinically node-negative (cN0) breast cancer. The application of SLN surgery for staging the axilla following chemotherapy for women who initially had node-positive cN1 breast cancer is unclear because of high false-negative results reported in previous studies.
  
  
  OBJECTIVE
  To determine the false-negative rate (FNR) for SLN surgery following chemotherapy in women initially presenting with biopsy-proven cN1 breast cancer.
  
  
  METHODS
  The American College of Surgeons Oncology Group (ACOSOG) Z1071 trial enrolled women from 136 institutions from July 2009 to June 2011 who had clinical T0 through T4, N1 through N2, M0 breast cancer and received neoadjuvant chemotherapy. Following chemotherapy, patients underwent both SLN surgery and ALND. Sentinel lymph node surgery using both blue dye (isosulfan blue or methylene blue) and a radiolabeled colloid mapping agent was encouraged.
  
  
  METHODS
  The primary end point was the FNR of SLN surgery after chemotherapy in women who presented with cN1 disease. We evaluated the likelihood that the FNR in patients with 2 or more SLNs examined was greater than 10%, the rate expected for women undergoing SLN surgery who present with cN0 disease.
  
  
  RESULTS
  Seven hundred fifty-six women were enrolled in the study. Of 663 evaluable patients with cN1 disease, 649 underwent chemotherapy followed by both SLN surgery and ALND. An SLN could not be identified in 46 patients (7.1%). Only 1 SLN was excised in 78 patients (12.0%). Of the remaining 525 patients with 2 or more SLNs removed, no cancer was identified in the axillary lymph nodes of 215 patients, yielding a pathological complete nodal response of 41.0% (95% CI, 36.7%-45.3%). In 39 patients, cancer was not identified in the SLNs but was found in lymph nodes obtained with ALND, resulting in an FNR of 12.6% (90% Bayesian credible interval, 9.85%-16.05%).
  
  
  CONCLUSIONS
  Among women with cN1 breast cancer receiving neoadjuvant chemotherapy who had 2 or more SLNs examined, the FNR was not found to be 10% or less. Given this FNR threshold, changes in approach and patient selection that result in greater sensitivity would be necessary to support the use of SLN surgery as an alternative to ALND.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00881361.
authors.affiliation: Department of Surgery, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Judy C
authors.initials: JC
authors.lastname: Boughey
authors.forename: Vera J
authors.initials: VJ
authors.lastname: Suman
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mittendorf
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Ahrendt
authors.forename: Lee G
authors.initials: LG
authors.lastname: Wilke
authors.forename: Bret
authors.initials: B
authors.lastname: Taback
authors.forename: A Marilyn
authors.initials: AM
authors.lastname: Leitch
authors.forename: Henry M
authors.initials: HM
authors.lastname: Kuerer
authors.forename: Monet
authors.initials: M
authors.lastname: Bowling
authors.forename: Teresa S
authors.initials: TS
authors.lastname: Flippo-Morton
authors.forename: David R
authors.initials: DR
authors.lastname: Byrd
authors.forename: David W
authors.initials: DW
authors.lastname: Ollila
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Julian
authors.forename: Sarah A
authors.initials: SA
authors.lastname: McLaughlin
authors.forename: Linda
authors.initials: L
authors.lastname: McCall
authors.forename: W Fraser
authors.initials: WF
authors.lastname: Symmans
authors.forename: Huong T
authors.initials: HT
authors.lastname: Le-Petross
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Haffty
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
authors.forename: Heidi
authors.initials: H
authors.lastname: Nelson
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Hunt
mesh_terms: D000328:Adult; D000368:Aged; D001365:Axilla; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D003102:Colloids; D004396:Coloring Agents; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008408:Mastectomy; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D019275:Radiopharmaceuticals; D021701:Sentinel Lymph Node Biopsy / Q000379:methods*; D055815:Young Adult
chemical_list: D003102:Colloids; D004396:Coloring Agents; D019275:Radiopharmaceuticals